Tanshinone I inhibits tumor angiogenesis by reducing STAT3 phosphorylation at TYR705 and hypoxia-induced HIF-1a accumulation in both endothelial and tumor cells

doi:10.18632/oncotarget.3648

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Tanshinone I inhibits tumor angiogenesis by reducing STAT3 phosphorylation at TYR705 and hypoxia-induced HIF-1a accumulation in both endothelial and tumor cells
	Wang, Yan 1,2; Li, Jia-Xin 1; Wang, Ying-Qing1 ; Miao, Ze-Hong 1
刊名	ONCOTARGET
	2015-06-30
卷号	6 期号:18 页码:16031-16042
关键词	tanshinone I angiogenesis Stat3 HIF-1 alpha VEGF
ISSN号	1949-2553
DOI	10.18632/oncotarget.3648
文献子类	Article
英文摘要	Tanshinone I (Tanshinone-1), a major active principle of Salvia miltiorrhiza (Danshen), has been shown to overcome tumor drug resistance and metastasis. Here we report that tanshinone-1 inhibits angiogenesis. Tanshinone-1 inhibited proliferation, migration and tube formation of vascular endothelial cells, rat aortic ring sprouting and the neovascularization of the chick chorioallantoic membrane in a concentration-dependent manner. In endothelial cells, tanshinone-1 almost completely inhibited phosphorylation of Stat3 at Tyr705 regardless of hypoxia or normoxia but only slightly decreased the hypoxia-induced HIF-1a accumulation. In tumor cells, contrastively, tanshinone-1 could not only make phosphorylation of Stat3 at Tyr705 disappear but also reduce the hypoxia-induced accumulation of HIF-1a to its baseline levels at normoxia. Consequently, VEGF secretion from tumor cells was reduced, which could potentiate the direct inhibition of tanshinone-1 on endothelial cells. Together with its overcoming tumor drug resistance and metastasis, our results reveal unique characteristics of tanshinone-1 and its improved derivatives as promising angiogenesis inhibitors.
资助项目	Science and Technology Commission of Shanghai Municipality[13XD1404200] ; National Basic Research Program of China[2012CB932502] ; National Science & Technology Major Project of China[2012ZX09301-001-002] ; National Natural Science Foundation of China[81321092] ; Program for Science and Technology Innovation of the Chinese Academy of Sciences[00000000] ; State Key Laboratory of Drug Research[00000000]
WOS关键词	BREAST-CANCER CELLS ; GROWTH ; EXPRESSION ; TRIPTOLIDE ; DEGRADATION ; ACTIVATION ; MECHANISMS ; THERAPY
WOS研究方向	Oncology ; Cell Biology
语种	英语
出版者	IMPACT JOURNALS LLC
WOS记录号	WOS:000359012000044
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276488]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Miao, Ze-Hong
作者单位	1.Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Nanchang Univ, Coll Pharm, Nanchang 330006, Peoples R China
推荐引用方式 GB/T 7714	Wang, Yan,Li, Jia-Xin,Wang, Ying-Qing,et al. Tanshinone I inhibits tumor angiogenesis by reducing STAT3 phosphorylation at TYR705 and hypoxia-induced HIF-1a accumulation in both endothelial and tumor cells[J]. ONCOTARGET,2015,6(18):16031-16042.
APA	Wang, Yan,Li, Jia-Xin,Wang, Ying-Qing,&Miao, Ze-Hong.(2015).Tanshinone I inhibits tumor angiogenesis by reducing STAT3 phosphorylation at TYR705 and hypoxia-induced HIF-1a accumulation in both endothelial and tumor cells.ONCOTARGET,6(18),16031-16042.
MLA	Wang, Yan,et al."Tanshinone I inhibits tumor angiogenesis by reducing STAT3 phosphorylation at TYR705 and hypoxia-induced HIF-1a accumulation in both endothelial and tumor cells".ONCOTARGET 6.18(2015):16031-16042.